ELOGA-IVF STUD: Comparative Effectiveness of Oral Elagolix Once Daily, Oral Elagolix Twice Daily, and Injectable Cetrorelix During Controlled Ovarian Stimulation in GnRH Antagonist IVF Cycles: A Retrospective Cohort Study

Introduction

Controlled ovarian stimulation requires effective suppression of premature LH surge to optimize mature oocyte retrieval. Injectable GnRH antagonists such as Cetrorelix are currently the standard of care. However, repeated injections increase treatment burden and overall treatment cost [1-3].

Elagolix is an oral non-peptide GnRH antagonist with rapid onset of pituitary suppression. Although currently approved for endometriosis and uterine fibroids in selected countries, its use during IVF stimulation remains off-label. Limited clinical data have evaluated oral elagolix as an alternative antagonist during IVF cycles [4-7].

This study aimed to compare clinical outcomes among three antagonist strategies used in routine practice.

Materials and Methods

Study Design

Single-center Retrospective observational cohort study.

Study Population

Medical records from January 2024 to December 2025 were screened.

A total of 402 IVF cycles met eligibility criteria.

                                                                                             Table 1: Group Allocation

Inclusion Criteria

• Age 22–38 years

• IVF/ICSI cycles

• GnRH antagonist protocol

• Complete medical records

• Complete embryology data

Exclusion Criteria

• Donor oocyte cycles

• PGT cycles

• Missing laboratory records

• Cycle cancellation before oocyte retrieval

• Severe liver disease

• Natural-cycle IVF

Outcomes

Primary Outcome

Number of MII oocytes retrieved.

Secondary Outcomes

• Total oocytes

• Fertilization rate

• Blastocyst formation rate

• Good-quality blastocyst rate

• Clinical pregnancy

• Trigger-day serum estradiol

• Trigger-day LH

• Premature LH surge

• OHSS

• Drug cost

• Number of antagonist injections

Statistical Analysis

a) Continuous variables were expressed as mean ± standard deviation.

b) Categorical variables were expressed as percentages.

c) Continuous variables were compared using one-way ANOVA.

d) Categorical variables were analyzed using Chi-square test.

e) Multivariable logistic regression adjusted for:

• Age

• BMI

• AMH

• AFC

• Gonadotropin dose

A p-value <0.05 was considered statistically significant.

Results

                                                                              Table 2: Baseline Characteristics

Ovarian Stimulation Outcomes

Hormonal Outcomes

Clinical Outcomes

Economic Analysis

Patients receiving oral Elagolix OD had the lowest medication cost and avoided daily antagonist injections.

Multivariable Analysis

After adjustment for age, BMI, AMH, AFC and gonadotropin dose, antagonist type was “not independently associated” with:

• Number of MII oocytes (β = −0.12; 95% CI −0.56 to 0.32; p = 0.59)

• Clinical pregnancy (adjusted OR 0.97; 95% CI 0.69–1.37; p = 0.88)

• Premature LH surge (adjusted OR 1.14; 95% CI 0.42–3.11; p = 0.79)

Discussion

In this retrospective cohort, ovarian stimulation outcomes were comparable among women receiving injectable Cetrorelix, oral elagolix twice daily, and oral elagolix once daily. No statistically significant differences were observed in mature oocyte yield, fertilization, blastocyst development, clinical pregnancy, or premature LH surge [5,6].

The once-daily elagolix regimen was associated with lower medication costs and eliminated the need for daily antagonist injections, potentially improving patient convenience and reducing treatment burden [6].

These findings suggest that oral elagolix 200 mg once daily may be a practical off-label alternative to injectable Cetrorelix in selected antagonist IVF cycles. However, because treatment allocation was based on physician discretion, residual confounding cannot be excluded [1,4-6].

Limitations

• Retrospective design.

• Single-center experience.

• Non-random treatment allocation.

• Off-label use of elagolix.

• Live birth data unavailable.

• Potential selection bias.

Conclusion

In this retrospective cohort, oral elagolix 200 mg once daily demonstrated ovarian stimulation, embryological, and clinical pregnancy outcomes comparable to oral elagolix twice daily and injectable Cetrorelix. The once-daily regimen substantially reduced medication cost and eliminated the need for daily antagonist injections. These findings support further prospective, multicenter randomized trials to validate the role of once-daily oral elagolix as an alternative GnRH antagonist during controlled ovarian stimulation.

Acknowledgement

Mr. Rizwan Abid, Senior Embryologist, Rashmika Fertility, India.

References

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2. Al-Inany, H. G., Youssef, M. A., Aboulghar, M., Broekmans,F. J., Sterrenburg, M. D., Smit, J. G., & Abou-Setta, A. M. (2011). Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database of Systematic Reviews, (5).
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7. Shebley, M., Polepally, A. R., Nader, A., Ng, J. W.,Winzenborg, I., Klein, C. E., ... & Mostafa, N. M. (2020). Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis:M. Shebley et al. Clinical pharmacokinetics, 59(3), 297-309.